Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas.
LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)-associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non-Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV-associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.


Happy creativity: Listening to happy music facilitates divergent thinking.
Creativity can be considered one of the key competencies for the twenty-first century. It provides us with the capacity to deal with the opportunities and challenges that are part of our complex and fast-changing world. The question as to what facilitates creative cognition-the ability to come up with creative ideas, problem solutions and products-is as old as the human sciences, and various means to enhance creative cognition have been studied. Despite earlier scientific studies demonstrating a beneficial effect of music on cognition, the effect of music listening on creative cognition has remained largely unexplored. The current study experimentally tests whether listening to specific types of music (four classical music excerpts systematically varying on valance and arousal), as compared to a silence control condition, facilitates divergent and convergent creativity. Creativity was higher for participants who listened to 'happy music' (i.e., classical music high on arousal and positive mood) while performing the divergent creativity task, than for participants who performed the task in silence. No effect of music was found for convergent creativity. In addition to the scientific contribution, the current findings may have important practical implications. Music listening can be easily integrated into daily life and may provide an innovative means to facilitate creative cognition in an efficient way in various scientific, educational and organizational settings when creative thinking is needed.


Prevalence of gastroesophageal reflux symptoms in adolescents: is there a difference in different racial and ethnic groups?
The study aims to determine if differences exist among racial/ethnic groups in the prevalence of gastroesophageal reflux symptoms in adolescents. A cross-sectional questionnaire was administered to a sample of students in four racially and ethnically diverse high schools in suburban Chicago. A total of 2561 questionnaires were analyzed: 33% Hispanics, 30% Caucasians, 22% African Americans, 15% Asians, 54% female, mean age 15.8 (±1.3) years. Thirty-two percent had at least one esophageal and/or respiratory symptom ≥once a week. Caucasians and African Americans had more dysphagia than Hispanics and Asians (7% vs. 4%; P= 0.04). Hispanics had more heartburn (13% vs. 9-11%; P= 0.06) but this was not statistically significant. There was no difference for regurgitation. Hispanic females had more dysphagia (6% vs. 3%; P= 0.02) and heartburn (17% vs. 9%; P= 0.0003) than Hispanic males. African Americans and Caucasians had more respiratory symptoms than Hispanics and Asians (29%, 24% vs. 18%; P= 0.000004). Students with esophageal symptoms were more likely to have respiratory symptoms (46% vs. 17%; P < 0.0005). African Americans and Caucasians with esophageal symptoms had more respiratory symptoms than Hispanics and Asians with esophageal symptoms (55%, 49% vs. 42%, 34%; P= 0.0003). Asians and Hispanics were less likely to treat symptoms than African Americans and Caucasians (26%, 33% vs. 47%, 49%; P= 0.001). We found that differences exist among the racial/ethnic groups with esophageal and respiratory symptoms; esophageal symptoms are a risk factor for respiratory symptoms, and Asians and Hispanics seek less medical help. Future research should focus on whether the differences found continue and reasons for them.


Demographic and other characteristics of nodal non-Hodgkin's lymphoma managed in academic versus non-academic centers.
Cancer therapy and outcomes are known to be affected by various demographic features and hospital types. We aimed to identify the characteristics of non-Hodgkin's lymphoma (NHL) patients associated with receipt of care at academic centers. This is a retrospective study of all patients diagnosed with nodal NHL between 2000 and 2011 in the National Cancer Database (NCDB), who received the diagnosis, and all or part of their initial therapy in the reporting hospital (n = 243,436). Characteristics of patients receiving care in academic versus nonacademic centers were compared using the Chi-square test. Approximately 27% received care in academic centers. Patients receiving care in nonacademic centers, compared with academic centers, were more likely to be ⩾60 years (69% versus 58%, p < .0001), White (89% versus 80%, p < .0001) and have lower educational attainment (>12% without high school diploma: 72% versus 69%, p < .0001) and economic status (household income <$49,000: 66% versus 61%, p < 0.0001). Patients receiving care in nonacademic centers were less likely to travel ⩾25 miles (21% versus 26%, p < 0.0001). White patients, compared with non-Whites, were more likely to be ⩾60 years (70% versus <50%, p < 0.0001), which probably explains less care in academic centers. Patients ⩾60 years and those with poorer educational attainment and economic status were less likely to receive care in academic centers. Care in academic centers required a longer commute. Elderly patients frequently have inferior outcomes and may benefit from clinical trials with novel agents and expertise at academic centers.


The unmet needs of partners and caregivers of adults diagnosed with cancer: a systematic review.
The recognition that a partner or caregiver is typically the patient's primary support person and is also deeply affected by the cancer diagnosis has prompted efforts to document their unmet supportive care needs. This review aimed to: (1) quantify the prevalence of unmet needs reported by partners and caregivers, (2) categorise their unmet needs by domain and (3) identify the main variables associated with reporting more unmet needs. Manuscripts were identified through systematically searching electronic databases, checking the reference lists of retrieved publications, online searching of key journals and contacting researchers in this field. Unmet need items across 29 manuscripts were clustered into six domains: comprehensive cancer care (prevalence 1.1%-96%), emotional and psychological (3%-93.2%), partner or caregiver impact and daily activities (2.8%-79%), relationship (3.7% and 58%), information (2.2%-86%) and spiritual (2%-43%). Studies of caregivers of palliative care or terminal patients often reported a higher prevalence of unmet needs than studies of caregivers of cancer survivors. Variables associated with higher unmet needs included being female, not being the spouse of the patient, having lower social support or reporting distress. Despite the ability to classify unmet needs within broad domains, quantification of unmet needs was challenging. This was mainly due to the diversity in methods used across studies (eg, different measures, variability in conceptualisation of unmet needs, etc). Rigorous, context-specific, longitudinal studies that use validated measures are needed to benefit future intervention research.


Increased transmission of Mycobacterium tuberculosis Beijing genotype strains associated with resistance to streptomycin: a population-based study.
Studies have shown that the Mycobacterium tuberculosis Beijing genotype is an emerging pathogen that is frequently associated with drug resistance. This suggests that drug resistant Beijing strains have a relatively high transmission fitness compared to other drug-resistant strains. We studied the relative transmission fitness of the Beijing genotype in relation to anti-tuberculosis drug resistance in a population-based study of smear-positive tuberculosis patients prospectively recruited and studied over a 4-year period in rural Vietnam. Transmission fitness was analyzed by clustering of cases on basis of three DNA typing methods. Of 2531 included patients, 2207 (87%) were eligible for analysis of whom 936 (42%) were in a DNA fingerprint cluster. The clustering rate varied by genotype with 292/786 (37%) for the Beijing genotype, 527/802 (67%) for the East-African Indian (EAI) genotype, and 117/619 (19%) for other genotypes. Clustering was associated with the EAI compared to the Beijing genotype (adjusted odds ratio (OR(adj)) 3.4: 95% CI 2.8-4.4). Patients infected with streptomycin-resistant strains were less frequently clustered than patients infected with streptomycin-susceptible strains when these were of the EAI genotype (OR(adj) 0.6, 95% CI 0.4-0.9), while this pattern was reversed for strains of the Beijing genotype (OR(adj) 1.3, 95% CI 1.0-1.8, p for difference 0.002). The strong association between Beijing and MDR-TB (OR(adj) 7.2; 95% CI 4.2-12.3) existed only if streptomycin resistance was present. Beijing genotype strains showed less overall transmissibility than EAI strains, but when comparisons were made within genotypes, Beijing strains showed increased transmission fitness when streptomycin-resistant, while the reverse was observed for EAI strains. The association between MDR-TB and Beijing genotype in this population was strongly dependent on resistance to streptomycin. Streptomycin resistance may provide Beijing strains with a fitness advantage over other genotypes and predispose to multidrug resistance in patients infected with Beijing strains.


Workshop cluster 1+ gammadelta T-cell receptor T cells from calves express high levels of interferon-gamma in response to stimulation with interleukin-12 and -18.
Gammadelta T-cell receptor(+) T lymphocytes are an important element of the innate immune system. Early production of interferon (IFN)-gamma by gammadelta T cells may have a role in linking innate and adaptive immune responses and contribute to T helper-1 bias. We investigated the role of cytokines in the activation and induction of IFN-gamma secretion by bovine workshop cluster 1(+) (WC1(+)) gammadelta T cells. The effects of culture with interleukin (IL)-12, IL-18, IL-15 and IL-2 were investigated; these cytokines are known to influence murine and human gammadelta T cells. We report that bovine WC1(+)gammadelta T cells are synergistically stimulated by IL-12 and IL-18 to secrete large quantities of IFN-gamma. Neonatal calves were shown to have significantly higher numbers of circulating WC1(+)gammadelta T cells than adult animals. In addition, the response of peripheral blood WC1(+)gammadelta T cells was significantly higher in neonatal calves compared with adult animals. However, in adult animals the response of lymph node WC1(+)gammadelta T cells to IL-12/IL-18 was more pronounced than that of peripheral blood WC1(+)gammadelta T cells. We hypothesize that the induction of IFN-gamma secretion from WC1(+)gammadelta T cells by IL-12 and IL-18 is likely to be an important element of the innate response to pathogens such as Mycobacterium bovis. The high numbers of WC1(+)gammadelta T cells in neonatal calves, and their inherent ability to respond to inflammatory cytokines, could be a key factor in the enhanced responses seen in calves to BCG vaccination.


Ameliorating effects of HX106N, a water-soluble botanical formulation, on Aβ25-35-induced memory impairment and oxidative stress in mice.
It is well-established that amyloid β (Aβ)-induced oxidative stress plays a crucial role in Alzheimer's disease (AD) and its cognitive deficits. HX106N is a water-soluble extract prepared from a mixture of the plants Dimocarpus longan, Liriope platyphylla, Salvia miltiorrhiza, and Gastrodia elata. These ingredients are traditionally used in various plant-based medicines for the treatment of neurological disease. In this study, we examined the effects of HX106N on memory impairment and oxidative stress caused by the intracerebroventricular injection of Aβ25-35 peptide in mice. For one week prior to Aβ25-35 peptide injection and 8 d after, mice were given oral HX106N. HX106N treatment reversed the Aβ25-35-mediated decrease in alternation percentage and latency time in the Y-maze and passive avoidance tests. Mice treated with HX106N showed decreased levels of thiobarbituric acid reactive substances (TBARS), a lipid peroxidation marker. Quantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated that HX106 treatment increased levels of heme oxygenase-1 (HO-1) in the hippocampus of Aβ25-35-injected mice, while having little effect on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In the murine hippocampal neuronal cell line HT22, HX106N was found to upregulate HO-1 expression at the RNA and protein levels as well as to protect cells from glutamate-induced oxidative stress. Taken together, our data suggest that HX106N may potentially act as a preventive and/or therapeutic agent for AD.


Simultaneous visualization and cell-specific confirmation of RNA and protein in the mouse retina.
Simultaneous dual labeling to visualize specific RNA and protein content within the same formalin-fixed paraffin embedded (FFPE) section can be technically challenging and usually impossible, because of variables such as tissue fixation time and pretreatment methods to access the target RNA or protein. Within a specific experiment, ocular tissue sections can be a precious commodity. Thus, the ability to easily and consistently detect and localize cell-specific expression of RNA and protein within a single slide would be advantageous. In this study, we describe a simplified and reliable method for combined in situ hybridization (ISH) and immunohistochemistry (IHC) for detection of mRNA and protein, respectively, within the same FFPE ocular tissue. Whole mouse eyes were prepared for 5 micron FFPE sections after fixation for 3, 24, 48 or 72 h. Customized probes from Advanced Cell Diagnostics to detect mRNA for vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1-alpha (HIF-1α), and hypoxia-inducible factor 2-alpha (HIF-2α) were used for ISH. Various parameters were tested using the novel RNAscope method for ISH and optimized for compatibility with subsequent IHC for glial fibrillary acidic protein (GFAP) or GS-lectin within the same tissue section. Dual fluorescent visualization of Fast Red ISH and Alexa Fluor 488 IHC signal was observed with confocal microscopy. A fixation time of 72 h was found to be optimal for ISH and subsequent IHC. The RNAscope probes for VEGF, HIF-1α, and HIF-2α mRNA all gave a strong Fast Red signal with both 48 h and 72 h fixed tissue, but the optimal IHC signal for either GFAP or GS-lectin within a retinal tissue section after ISH processing was observed with 72 h fixation. A pretreatment boiling time of 15 min and a dilution factor of 1:15 for the pretreatment protease solution were found to be optimal and necessary for successful ISH visualization with 72 h FFPE ocular tissue. The protocol presented here provides a simple and reliable method to simultaneously detect mRNA and protein within the same paraffin-embedded ocular tissue section. The procedure, after preparation of FFPE sections, can be performed over a 2-day or 4-day period. We provide an optimization strategy that may be adapted for any RNAscope probe set and antibody for determining retinal or ocular cell-specific patterns of expression.


Hypoxia Differentially Regulates Arterial and Venous Smooth Muscle Cell Migration.
Intimal hyperplasia (IH) is a clinical concern leading to failure of up to 50% of vein grafts and 10% of arterial grafts after 10 years with no known current treatment. Recent studies have shown that hypoxia differentially regulates proliferation of vein derived smooth muscle cells (V-SMC) compared to artery derived smooth muscle cells (A-SMC). The objective of this study is to evaluate the effect of hypoxia on cellular migration and the mechanisms underlying the differential effects of hypoxia on A-SMC and V-SMC migration. Hypoxic treatment (3-5% O2) of Smooth Muscle Cells (SMC) resulted in differential migration in scratch wound and electric cell substrate impedance sensing (ECIS) assays. Hypoxia led to greater migration compared to normoxia with venous derived wound closure (V-SMC 30.8% Normoxia to 67% Hypoxia) greater than arterial wound closure (A-SMC 6.2% Normoxia to 24.7% Hypoxia). Paracrine factors secreted by hypoxic endothelial cells induced more migration in SMC compared to factors secreted by normoxic endothelial cells. Migration of V-SMC was greater than A-SMC in the presence of paracrine factors. Neutralizing antibody to Vascular Endothelial Growth Factor Receptor -1 (VEGFR-1) completely inhibited V-SMC migration while there was only partial inhibition of A-SMC migration. A-SMC migration was completely inhibited by Platelet Derived Growth Factor BB (PDGF-BB) neutralizing antibody. p38 Mitogen Activated Protein kinase (p38 MAPK) inhibitor pre-incubation completely inhibited migration induced by paracrine factors in both A-SMC and V-SMC. Our study determines that SMC migration under hypoxia occurs via both an autocrine and paracrine mechanism and is dependent on Vascular Endothelial Growth Factor-A (VEGF-A) in V-SMC and PDGF-BB in A-SMC. Migration of both A-SMC and V-SMC is inhibited by p38 MAPK inhibitor. These studies suggest that pharmacotherapeutic strategies directed at modulating p38 MAPK activity can be exploited to prevent IH in vascular grafts.


Noninvasive radiofrequency treatment effect on mitochondria in pancreatic cancer cells.
The development of novel therapeutic approaches for cancer therapy is important, especially for tumors that have poor response or develop resistance to standard chemotherapy and radiation. We discovered that noninvasive radiofrequency (RF) fields can affect cancer cells but not normal cells, inhibit progression of tumors in mice, and enhance the anticancer effects of chemotherapy. However, it remains unclear what physiological and molecular mechanisms this treatment induces inside cells. Here, we studied the effect of RF treatment on mitochondria in human pancreatic cancer cells. The morphology of mitochondria in cells was studied via electron microscopy. The alteration of mitochondrial membrane potential (Δψ) was accessed using a Mitotracker probe. The respiratory activity of mitochondria was evaluated by analyzing changes in oxygen consumption rates determined with a Mito Stress Test Kit. The production of intracellular reactive oxygen species was performed using flow cytometry. The colocalization of mitochondria and autophagosome markers in cells was performed using fluorescence immunostaining and confocal microscopy analysis. RF fields treatment changed the morphology of mitochondria in cancer cells, altered polarization of the mitochondrial membrane, substantially impaired mitochondrial respiration, and increased reactive oxygen species production, indicating RF-induced stress on the mitochondria. We also observed frequent colocalization of the autophagosome marker LC3B with the mitochondrial marker Tom20 inside cancer cells after RF exposure, indicating the presence of mitochondria in the autophagosomes. This suggests that RF-induced stress can damage mitochondria and induce elimination of damaged organelles via autophagy. RF treatment impaired the function of mitochondria in cancer cells. Therefore, mitochondria can represent one of the targets of the RF treatment.


The impact of team empowerment on proactivity: the moderating roles of leader's emotional intelligence and proactive personality.
The purpose of this study is to investigate the relationship between team empowerment and team proactivity and the moderating roles of a team leader's emotional intelligence (EI) and a team member's proactive personality. To provide a rigorous test of the hypotheses, a field study from a sample of 910 certified nurses in 82 teams from 12 university hospitals in Turkey was conducted. The results reveal that proactivity is positively associated with team empowerment. In addition, team leader's EI and team members' proactive personality influence the relationship between team empowerment and team proactivity. Specifically, teams exhibit the highest proactivity when team leaders' EI and team members' proactive personality are high. The main strength of the investigation in this study was its multilevel research design. Most research on proactivity and empowerment has been conducted within single organizations, precluding an assessment of the way in which individual difference variables influence empowerment or proactivity. The multilevel design incorporated in this study, however, was capable of capturing the complexity of individual behaviors by considering different contexts. In encouraging team proactivity, leadership and team members' personality characteristics do matter. Identifying individual difference variables such as team leader's EI, leader-member exchange, locus of control or team members' personality help to advance the theoretical understanding of the team proactivity. This study provides evidence of the positive relationship between team empowerment and team proactivity. Such knowledge may help to search for continuous improvement and innovative solutions to work problems employed by healthcare administrators and potentially reduce the costs associated with losing high-potential nurses. This is one of the first studies to provide evidence of the moderating roles of the team leader's EI and team members' proactive personality levels on the relationship between team empowerment and team proactivity in university hospitals that formally implement work teams.


Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY.
To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged ≥45 years and have experienced knee pain ≥4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. Australian New Zealand Clinical Trials Registry: ACTRN12617001595303 , date of registration 1/12/2017.


The prevalence of chronic pelvic pain in women in the United Kingdom: a systematic review.
To obtain a prevalence estimate for chronic pelvic pain in women in the United Kingdom by analysing published data. Systematic review of published papers. The general population or hospitals in the United Kingdom. Women participating in relevant community surveys or control women participating in hospital-based studies. Papers were retrieved by systematically searching the databases MEDLINE, EMBASE and PsycLit, and by hand searching. Studies were included if they 1. were community-based and reported prevalence rates of chronic pelvic pain, dyspareunia, dysmenorrhoea, or abdominal pain, or 2. referred to a clinical population but reported prevalence rates in a disease-free control group. Prevalence rates for chronic pelvic pain including any overlap with dyspareunia, dysmenorrhoea and abdominal pain. No community-based study has been performed that provides an estimate of the prevalence of chronic pelvic pain in the general UK population. A rate of 39% was reported in women undergoing laparoscopy for sterilisation or investigation of infertility in the single study from the United Kingdom investigating chronic pelvic pain unrelated to menstruation or intercourse. Prevalence rates for dyspareunia, dysmenorrhoea, and abdominal pain found in UK community-based studies were 8%, 45% to 97%, and 23% to 29%, respectively, but definitions used varied greatly. Because chronic pelvic pain can reduce the quality of life and general wellbeing, there is a need for a community-based study into the prevalence of chronic pelvic pain and its effect upon the lives of women in the UK.


Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis.
Our purpose was to determine whether abdominal CT can detect pancreatic cancer before its clinical diagnosis. Two radiologists interpreted in a blinded manner 62 CT scans in 28 pancreatic cancer patients that were obtained before histologic diagnosis and 89 CT scans in 89 control subjects and noted specific CT findings. The presence of pancreatic cancer was characterized as definite, suspicious, low probability, or normal. The scans of the pancreatic cancer patients were divided into four groups on the basis of the time interval preceding cancer diagnosis (0-2, 2-6, 6-18, or > 18 months), and one scan (closest to 18 months) was selected per patient per time interval. Sensitivity and specificity for pancreatic cancer and interobserver agreement for CT findings were calculated. Radiologists agreed that CT findings definite or suspicious for pancreatic cancer were present in 50% of the scans obtained 2-6 and 6-18 months before the diagnosis of pancreatic cancer (3/6 and 4/8 scans, respectively), but they noted such CT findings in only 7% (1/15) of the scans obtained more than 18 months before diagnosis. Pancreatic duct dilatation and cutoff were early CT findings identified by both radiologists and were associated with near-perfect and substantial interobserver agreement (kappa = 0.84 and 0.76, respectively). Ninety-five percent confidence intervals of specificity for tumor absence ranged from 92% to 100%. CT can detect a significant proportion of asymptomatic incident pancreatic cancers before the clinical diagnosis of pancreatic cancer. CT should be considered in screening at-risk patient populations. Pancreatic duct dilatation and cutoff are early findings associated with the development of pancreatic cancer and can be detected on CT with a high degree of reproducibility.


Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study.
Persons with schizophrenia die earlier than the general population, in large part due to cardiovascular disease. The study objective was to examine effects of different antipsychotic treatments on estimates of 10-year coronary heart disease (CHD) risk calculated by the Framingham Heart Study formula. Change in 10-year risk for CHD was compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial. The covariate-adjusted mean change in 10-year CHD risk differed significantly between treatments. Olanzapine was associated with a 0.5% (SE 0.3) increase and quetiapine, a 0.3% (SE 0.3) increase; whereas risk decreased in patients treated with perphenazine, -0.5% (SE 0.3), risperidone, -0.6% (SE 0.3), and ziprasidone -0.6% (SE 0.4). The difference in 10-year CHD risk between olanzapine and risperidone was statistically significant (p=0.004). Differences in estimated 10-year CHD risk between drugs were most marked in the tertile of subjects with a baseline CHD risk of at least 10%. Among individual CHD risk factors used in the Framingham formula, only total and HDL cholesterol levels differed between treatments. These results indicate that the impact on 10-year CHD risk differs significantly between antipsychotic agents, with olanzapine producing the largest elevation in CHD risk of the agents studied in CATIE.


Neural activation to emotional faces in adolescents with autism spectrum disorders.
Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing in adolescents with ASD. Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250 ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face. The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p < .05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task. When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing.


Femoral central venous catheters are not associated with higher rates of infection in the pediatric critical care population.
Adult data show a difference in central venous catheter (CVC) infection rates between 3 major sites: subclavian (SC), internal jugular (IJ), and femoral veins. We hypothesized that in patients in pediatric intensive care units (PICUs), there is no difference in rates of CVC infection among these three sites, but specifically the femoral compared to all other sites. In this retrospective cohort study, data from January 1999 to January 2008 were collected prospectively for internal review and quality assurance. All PICU patients with a CVC were enrolled. The rate of CVC infection was determined using Cox regression survival analysis to account for various durations of CVC placement at the various sites, then adjusted for severity of illness, number of lumens, and patient age. Mortality was compared in patients with a CVC infection versus those without. A total of 4,512 patients with a CVC were enrolled. No site was associated with an increased risk of infection compared with the other sites, with hazard ratios of 0.951 (95% confidence interval [CI], 0.612-1.478) for the SC site, 0.956 (95% CI, 0.593-1.541) for the IJ site, and 1.120 (95% CI, 0.753-1.665) for the femoral site. No significant association between mortality and presence of CVC infection was found when adjusted for age, severity of illness, and duration of CVC placement. An association was found between the presence of a CVC infection and prolonged PICU length of stay (3.98 days longer; P < .001). Femoral CVCs are not associated with higher rates of infection in the PICU. In addition, the presence of CVC infection does not affect mortality, but is associated with longer PICU admission.


Isolation of Arcobacter species and other neglected opportunistic agents from aborted bovine and caprine fetuses.
Infectious abortion in ruminants is a problem in animal husbandry worldwide. It is important to obtain a diagnosis, to make sure that proper control measures can be instituted, but most abortion cases remain without an etiologic diagnosis. This report describes the presence of Arcobacter species and several neglected opportunistic abortifacient agents in ruminant abortion cases showing or not co-infections among at least one of the major recognized protozoal, fungal, bacterial and viral abortifacient agents. A total of 67 fetuses (55 cattle and 12 goats) and just one placenta (cattle) were considered. Among the most common abortive agents, Neospora caninum (19,4%), followed by Chlamydophila abortus (4,5%), Listeria monocytogenes 1/2a (2,98%), Bovine Viral Diarrhea Virus type 1b (2,98%), Bovine herpesvirus 4 (2,98%), and Aspergillus spp. (2,98%) were detected. The isolated neglected opportunistic bacteria include Escherichia coli, Acinetobacter lwoffii, Staphylococcus spp., Streptococcus spp., Streptococcus uberis, Streptococcus suis, Trueperella pyogenes, Mannheimia haemolytica, Bacillus cereus and Nocardia spp. Other bacterial species, not associated with abortion by literature, but described as causes of diseases occurring sporadically both in humans and animals, were also detected. Three Arcobacter strains, namely two A. skirrowii and one A. cryaerophilus, were isolated from 3 bovine aborted fetuses, and A. butzleri was isolated from the placenta. A not negligible isolation of Arcobacter species and other neglected abortifacient agents has to be mentioned, with prevalences that seem to be emerging and replacing or co-placing the major infectious players in bovine and caprine reproductive failure due to abortion disease, even if further studies investigating the aetiological power and transmission routes are needed in order to define the role of these microrganisms in ruminant abortion.


[A robust classification method for five types of leukocytes in peripheral blood based on mean-shift clustering].
A new leukocyte classification method for recognition of five types of human peripheral blood smear based on mean-shift clustering is proposed. The key idea of the proposed method is to extract the texture features of leukocytes in a visual manner which can benefit from human eyes. Firstly, some feature points are extracted in a gray leukocyte image by mean-shift. Secondly, these feature points are used as seeds of the region growing to expand feature regions which can express texture in visual mode to a certain extent. Finally, a parameter vector of these regions is extracted as the texture feature. Combing the vector with the geometric features of the leukocyte, the five typical classes of leukocytes can be recognized successfully using artificial neural network (ANN). A total number of 1 310 leukocyte images have been tested and the accurate rate of recognition for neutrophil, eosinophil, basophil, lymphocyte and monocyte are 95.4%, 93.8%, 100%, 93.1% and 92.4%, respectively, which shows the feasibility and high robustness of the proposed method.


The ventilation problem in schools: literature review.
Based on a review of literature published in refereed archival journals, ventilation rates in classrooms often fall far short of the minimum ventilation rates specified in standards. There is compelling evidence, from both cross-sectional and intervention studies, of an association of increased student performance with increased ventilation rates. There is evidence that reduced respiratory health effects and reduced student absence are associated with increased ventilation rates. Increasing ventilation rates in schools imposes energy costs and can increase heating, ventilating, and air-conditioning system capital costs. The net annual costs, ranging from a few dollars to about 10 dollars per person, are less than 0.1% of typical public spending on elementary and secondary education in the United States. Such expenditures seem like a small price to pay given the evidence of health and performance benefits.


Progression of aortic arch calcification over 1 year is an independent predictor of mortality in incident peritoneal dialysis patients.
The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (AoAC) and prognostic value of AoAC progression in PD patients. We prospectively determined AoAC by chest X-ray at PD start and after 12 months, and evaluated the impact of AoAC progression on mortality in 415 incident PD patients. Of 415 patients, 169 patients (40.7%) had AoAC at baseline with a mean of 18.1±11.2%. The presence of baseline AoAC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336-3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577-8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with AoAC progression was significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P<0.001). Multivariate Cox analysis revealed that AoAC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150-5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079-14.890, P = 0.038) in patients with AoAC at baseline. The presence and progression of AoAC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients.


Indacenodibenzothiophenes: synthesis, optoelectronic properties and materials applications of molecules with strong antiaromatic character.
Indeno[1,2-b]fluorenes (IFs), while containing 4n π-electrons, are best described as two aromatic benzene rings fused to a weakly paratropic s-indacene core. In this study, we find that replacement of the outer benzene rings of an IF with benzothiophenes allows the antiaromaticity of the central s-indacene to strongly reassert itself. Herein we report a combined synthetic, computational, structural, and materials study of anti- and syn-indacenodibenzothiophenes (IDBTs). We have developed an efficient and scalable synthesis for preparation of a series of aryl- and ethynyl-substituted IDBTs. NICS-XY scans and ACID calculations reveal an increasingly antiaromatic core from [1,2-b]IF to anti-IDBT, with syn-IDBT being nearly as antiaromatic as the parent s-indacene. As an initial evaluation, the intermolecular electronic couplings and electronic band structure of a diethynyl anti-IDBT derivative reveal the potential for hole and / or electron transport. OFETs constructed using this molecule show the highest hole mobilities yet achieved for a fully conjugated IF derivative.


Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats.
Traumatic brain injury (TBI) initiates a complex series of neurochemical and signaling changes that lead to pathological events including neuronal hyperactivity, excessive glutamate release, inflammation, increased blood-brain barrier (BBB) permeability and cerebral edema, altered gene expression, and neuronal dysfunction. It is believed that a drug combination, or a single drug acting on multiple targets, may be an effective strategy to treat TBI. Valproate, a widely used antiepileptic drug, has a number of targets including GABA transaminase, voltage-gated sodium channels, glycogen synthase kinase (GSK)-3, and histone deacetylases (HDACs), and therefore may attenuate a number of TBI-associated pathologies. Using a rodent model of TBI, we tested if post-injury administration of valproate can decrease BBB permeability, reduce neural damage and improve cognitive outcome. Dose-response studies revealed that systemic administration of 400 mg/kg (i.p.), but not 15, 30, 60 or 100 mg/kg, increases histone H3 and H4 acetylation, and reduces GSK-3 activity, in the hippocampus. Thirty min post-injury administration of 400 mg/kg valproate improved BBB integrity as indicated by a reduction in Evans Blue dye extravasation. Consistent with its dose response to inhibit GSK-3 and HDACs, valproate at 400 mg/kg, but not 100 mg/kg, reduced TBI-associated hippocampal dendritic damage, lessened cortical contusion volume, and improved motor function and spatial memory. These behavioral improvements were not observed when SAHA (suberoylanilide hydroxamic acid), a selective HDAC inhibitor, was administered. Our findings indicate that valproate given soon after TBI can be neuroprotective. As clinically proven interventions that can be used to minimize the damage following TBI are not currently available, the findings from this report support the further testing of valproate as an acute therapeutic strategy.


Levodopa: effect on cell death and the natural history of Parkinson's disease.
This review article considers the question of whether or not levodopa is toxic in Parkinson's disease (PD). l-dopa is the most effective symptomatic treatment for PD and has provided benefit for millions of patients. However, there has been a longstanding concern that l-dopa might be toxic and accelerate neuronal degeneration and clinical progression as a consequence of reactive oxygen species generated by the drug's oxidative metabolism. In vitro, l-dopa can induce degeneration of dopaminergic neurons, but it is not clear that the effects of the drug on cultured dopamine neurons reflect what happens in the PD brain. In vivo, l-dopa has not been demonstrated to have toxic effects on dopamine neurons in normal, dopamine-lesioned, or oxidatively stressed animal models, but none of these models precisely replicates the PD condition. Clinical trials have tested the effect of l-dopa on clinical progression and have not demonstrated any findings indicative of toxicity. However, the symptomatic and long-duration effects of the drug could mask ongoing neuronal degeneration. Furthermore, l-dopa induces a greater decline in imaging measures of dopaminergic function than placebo or dopamine agonists, consistent with toxicity. Pathological studies have not demonstrated evidence of accelerated loss of dopamine neurons, but prospective and properly controlled studies with stereological unbiased counting have not been performed. Thus, although there is no hard evidence to suggest that l-dopa is toxic in PD patients, the issue has not been fully resolved. It is generally recommended that physicians continue to use l-dopa, but in the lowest dose that provides satisfactory clinical control.


Involvement of the superior temporal cortex and the occipital cortex in spatial hearing: evidence from repetitive transcranial magnetic stimulation.
The processing of auditory spatial information in cortical areas of the human brain outside of the primary auditory cortex remains poorly understood. Here we investigated the role of the superior temporal gyrus (STG) and the occipital cortex (OC) in spatial hearing using repetitive transcranial magnetic stimulation (rTMS). The right STG is known to be of crucial importance for visual spatial awareness, and has been suggested to be involved in auditory spatial perception. We found that rTMS of the right STG induced a systematic error in the perception of interaural time differences (a primary cue for sound localization in the azimuthal plane). This is in accordance with the recent view, based on both neurophysiological data obtained in monkeys and human neuroimaging studies, that information on sound location is processed within a dorsolateral "where" stream including the caudal STG. A similar, but opposite, auditory shift was obtained after rTMS of secondary visual areas of the right OC. Processing of auditory information in the OC has previously been shown to exist only in blind persons. Thus, the latter finding provides the first evidence of an involvement of the visual cortex in spatial hearing in sighted human subjects, and suggests a close interconnection of the neural representation of auditory and visual space. Because rTMS induced systematic shifts in auditory lateralization, but not a general deterioration, we propose that rTMS of STG or OC specifically affected neuronal circuits transforming auditory spatial coordinates in order to maintain alignment with vision.


Metabolite Profiling of Sugarcane Genotypes and Identification of Flavonoid Glycosides and Phenolic Acids.
Sugarcane is an important agricultural crop in the economy of tropical regions, and Brazil has the largest cultivated acreage in the world. Sugarcane accumulates high levels of sucrose in its stalks. Other compounds produced by sugarcane are currently not of economic importance. To explore potential coproducts, we have studied the chemical diversity of sugarcane genotypes, via metabolite profiling of leaves by NMR and LC-DAD-MS. Metabolites were identified via in-house and public databases. From the analysis of 60 HPLC-fractionated extracts, LC-DAD-MS detected 144 metabolites, of which 56 were identified (MS-MS and (1)H NMR), including 19 phenolics and 25 flavones, with a predominance of isomeric flavone C-glycosides. Multivariate analysis of the profiles from genotypes utilized in Brazilian breeding programs revealed clustering according to sugar, phenolic acid, and flavone contents.


Green synthesis of near infrared core/shell quantum dots for photocatalytic hydrogen production.
Quantum dots (QDs) are attractive systems for potential applications in future solar energy technologies, due to their optical properties which are tunable as a function of size and composition. In this study, we synthesized PbS QDs with first excitonic peak in the range 1060 to 1300 nm using a PbCl2/sulfur molar ratio of 10:1. The first excitonic absorption peak from 1300 to 950 nm of the PbS/CdS core/shell QDs can be further synthesized via the cation exchange approach. Our method resulted in high quantum yield, good stability, monodisperse QD solutions with a full surface coverage by excess Cd cations. In addition, we used our core/shell QDs in a photoelectrochemical cell for hydrogen generation. This heterostructure exhibited a saturated photocurrent as high as 3.3 mA cm-2, leading to ∼29 ml cm-2 d-1 hydrogen generation, indicating the strong potential of our core/shell QDs for applications in water splitting.


Occupational health outcomes among international migrant workers: a systematic review and meta-analysis.
Globally, there are more than 150 million international migrant workers-individuals who are employed outside of their country of origin-comprising the largest international migrant group. A substantial number of migrants work in hazardous and exploitative environments, where they might be at considerable risk of injury and ill health. However, little data on occupational health outcomes of migrant workers exist, with which to inform global policy making and delivery of health services. For this systematic review and meta-analysis, we searched Embase, MEDLINE, Ovid Global Health, and PsychINFO databases for primary research published between Jan 1, 2008, and Jan 24, 2018, reporting occupational health outcomes among international migrant workers (defined as individuals who are or have been employed outside their country of origin), without language or geographical restrictions. We excluded studies containing mixed cohorts of migrants and native workers in which migrant data could not be disaggregated, and studies that did not explicitly report migrant status. The main outcome was prevalence of occupational health outcomes (defined as any injury, mortality, or physical or psychiatric morbidity due to an individual's work or workplace environment) among international migrant workers. Summary estimates were calculated using random-effects models. The study protocol has been registered with PROSPERO, number CRD42018099465. Of the 1218 studies identified by our search, 36 studies were included in our systematic review, and 18 studies were included in the meta-analysis. The systematic review included occupational health outcomes for 12 168 international migrant workers employed in 13 countries and territories, mostly employed in unskilled manual labour. Migrant workers originated from 25 low-income and middle-income countries, and worked in the following sectors: agriculture; domestic, retail, and service sectors; construction and trade; and manufacturing and processing. Migrant workers had various psychiatric and physical morbidities, and workplace accidents and injuries were relatively common. In the meta-analysis, among 7260 international migrant workers, the pooled prevalence of having at least one occupational morbidity was 47% (95% CI 29-64; I2=99·70%). Among 3890 migrant workers, the prevalence of having at least one injury or accident, including falls from heights, fractures and dislocations, ocular injuries, and cuts was 22% (7-37; I2=99·35%). International migrant workers are at considerable risk of work-related ill health and injury, and their health needs are critically overlooked in research and policy. Governments, policy makers, and businesses must enforce and improve occupational health and safety measures, which should be accompanied by accessible, affordable, and appropriate health care and insurance coverage to meet the care needs of this important working population. Wellcome Trust.


Human platelet lysates for human cell propagation.
A pathogen-free and standardized xeno-free supplement of growth media is required for the ex vivo propagation of human cells used as advanced therapeutic medicinal products and for clinical translation in regenerative medicine and cell therapies. Human platelet lysate (HPL) made from therapeutic-grade platelet concentrate (PC) is increasingly regarded as being an efficient xeno-free alternative growth medium supplement to fetal bovine serum (FBS) for clinical-grade isolation and/or propagation of human cells. Most experimental studies establishing the superiority of HPL over FBS were conducted using mesenchymal stromal cells (MSCs) from bone marrow or adipose tissues. Data almost unanimously concur that MSCs expanded in a media supplemented with HPL have improved proliferation, shorter doubling times, and preserved clonogenicity, immunophenotype, in vitro trilineage differentiation capacity, and T-cell immunosuppressive activity. HPL can also be substituted for FBS when propagating MSCs from various other tissue sources, including Wharton jelly, the umbilical cord, amniotic fluid, dental pulp, periodontal ligaments, and apical papillae. Interestingly, HPL xeno-free supplementation is also proving successful for expanding human-differentiated cells, including chondrocytes, corneal endothelium and corneal epithelium cells, and tenocytes, for transplantation and tissue-engineering applications. In addition, the most recent developments suggest the possibility of successfully expanding immune cells such as macrophages, dendritic cells, and chimeric antigen receptor-T cells in HPL, further broadening its use as a growth medium supplement. Therefore, strong scientific rationale supports the use of HPL as a universal growth medium supplement for isolating and propagating therapeutic human cells for transplantation and tissue engineering. Efforts are underway to ensure optimal standardization and pathogen safety of HPL to secure its reliability for clinical-grade cell-therapy and regenerative medicine products and tissue engineering.


Is surgery in acute aortic dissection type A still contraindicated in the presence of preoperative neurological symptoms?
Severe neurological deficit (ND) due to acute aortic dissection type A (AADA) was considered a contraindication for surgery because of poor prognosis. Recently, more aggressive indication for surgery despite neurological symptoms has shown acceptable postoperative clinical results. The aim of this study was to evaluate early and mid-term outcomes of patients with AADA presenting with acute ND. Data from 53 patients with new-onset ND who received surgical repair for AADA between 2005 and 2012 at our institution were retrospectively reviewed. ND was defined as focal motor or sensory deficit, hemiplegia, paraplegia, convulsions or coma. Neurological symptoms were evaluated preoperatively using the Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS), and at discharge as well as 3-6 months postoperatively using the mRS and National Institutes of Health Stroke Scale. Involvement of carotid arteries was assessed in the pre- and postoperative computed tomography. Logistic regression analysis was performed to detect predictive factors for recovery of ND. Of the 53 patients, 29 (54.7%) showed complete recovery from focal ND at follow-up. Neurological symptoms persisted in 24 (45.3%) patients, of which 8 (33%) died without neurological assessment at follow-up. Between the two groups (patients with recovery and those with persisting ND), there was no significant difference regarding the duration of hypothermic circulatory arrest (28 ± 14 vs 36 ± 20 min) or severely reduced consciousness (GCS <8). Multivariate analysis showed significant differences for the preoperative mRS between the two groups (P < 0.007). A high preoperative mRS was associated with persistence of neurological symptoms (P < 0.02). Cardiovascular risk factors, age or involvement of supra-aortic branches were not predictive for persistence of ND. More than half of our patients recovered completely from ND due to AADA after surgery. Severity of clinical symptoms had a predictive value. Patients suffering from AADA and presenting with ND before surgery should not be excluded from emergency surgery.


Analysis of surface-plasmon-polaritons-assisted interference imaging by using silver film with rough surface.
In the surface plasmon polaritons (SPPs) interference lithography, the scattering effect caused by the rough surface of silver film deteriorates the quality of lithography patterns. Research shows that under this condition the light field in the photoresist is not the results of SPPs interference but comes from the SPPs assisted imaging in which the scattered light propagates from the upper surface of the silver film to the photoresist. The near-field optical transfer function (NOTF) is used to study this process and a method of evaluating the imaging quality is presented. The validity of NOTF is verified by both SPPs assisted interference imaging experiments and simulations by the FDTD. It is also shown that the NOTF method is not only a convenient approach to describe the nano-scale information transmission in the near-field but also a good method to optimize experimental parameters.


Development of portable mass spectrometer with electron cyclotron resonance ion source for detection of chemical warfare agents in air.
A portable mass spectrometer with an electron cyclotron resonance ion source (miniECRIS-MS) was developed. It was used for in situ monitoring of trace amounts of chemical warfare agents (CWAs) in atmospheric air. Instrumental construction and parameters were optimized to realize a fast response, high sensitivity, and a small body size. Three types of CWAs, i.e., phosgene, mustard gas, and hydrogen cyanide were examined to check if the mass spectrometer was able to detect characteristic elements and atomic groups. From the results, it was found that CWAs were effectively ionized in the miniECRIS-MS, and their specific signals could be discerned over the background signals of air. In phosgene, the signals of the 35Cl+ and 37Cl+ ions were clearly observed with high dose-response relationships in the parts-per-billion level, which could lead to the quantitative on-site analysis of CWAs. A parts-per-million level of mustard gas, which was far lower than its lethal dosage (LCt50), was successfully detected with a high signal-stability of the plasma ion source. It was also found that the chemical forms of CWAs ionized in the plasma, i.e., monoatomic ions, fragment ions, and molecular ions, could be detected, thereby enabling the effective identification of the target CWAs. Despite the disadvantages associated with miniaturization, the overall performance (sensitivity and response time) of the miniECRIS-MS in detecting CWAs exceeded those of sector-type ECRIS-MS, showing its potential for on-site detection in the future.


Design, synthesis and evaluation of analogs of initiation factor 4E (eIF4E) cap-binding antagonist Bn7-GMP.
Aberrant regulation of cap-dependent translation has been frequently observed in the development of cancer. Association of the cap-binding protein eIF4E with N(7)-methylated guanosine capped mRNA is the rate limiting step governing translation initiation; and therefore represents an attractive process for cancer drug discovery. Previously, replacement of the 7-Me group of the Me(7)-guanosine monophosphate with a benzyl group has been found to increase binding affinity to eIF4E. Recent X-ray crystallographic studies have revealed that the cap-binding pocket undergoes a unique structural change in order to accommodate the benzyl group. To explore the structure-activity relationships governing the affinity of N(7)-benzylated guanosine monophosphate (Bn(7)-GMP) for eIF4E, we virtually screened a library of 80 Bn(7)-GMP analogs utilizing CombiGlide as implemented in Schrodinger. A subset library of substituted Bn(7)-GMP analogs was synthesized and their dissociation constants (K(d)) were determined. Due to the poor correlation between docking/scoring results and experimental binding affinities, three-dimensional quantitative structure-activity relationship (3D-QSAR) calculations were performed. Two highly predictive and self-consistent CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) models were derived and optimized. These models may be useful for the future design of eIF4E cap-binding antagonists.


Rhizobium meliloti competitiveness and the alfalfa agglutinin.
We have isolated two types of isolates having identical colony morphologies from stock cultures of two different Rhizobium meliloti strains. One isolate was agglutinated at a high-dilution titer (HA, highly agglutinable) of the alfalfa agglutinin and was sensitive to phage F20, and the other was agglutinated at a lower agglutinin titer (LA) and was sensitive to phage 16B. All LA isolates from the original slant produced nodules on alfalfa earlier than did HA strains from the original slant. When these HA and LA strains were mixed and used as the inoculum in both vermiculite and field soil in the laboratory, LA strains were always the predominant strains recovered from the nodules. LA strains were obtained from HA cells by selection for resistance to phage F20, and HA strains were obtained from LA cells by selection for resistance to phage 16B. All of the strains with the HA phenotype that were derived from LA strains by phage selection had the nodulation properties of the HA strains from the original slant. Two classes of strains with the LA phenotype were obtained from HA cells by phage selection. One was identical to the original LA strains from the slant, and the other had the nodulation properties of the HA strains. Thus, we have shown that some cell surface properties change the nodulation abilities of R. meliloti strains and, furthermore, that specific phages can be used to enrich for more competitive rhizobia.


Anisotropic effective permittivity of an ultrathin gold coating on optical fiber in air, water and saline solutions.
The optical properties of an ultrathin discontinuous gold film in different dielectric surroundings are investigated experimentally by measuring the polarization-dependent wavelength shifts and amplitudes of the cladding mode resonances of a tilted fiber Bragg grating. The gold film was prepared by electron-beam evaporation and had an average thickness of 5.5 nm ( ± 1 nm). Scanning electron imaging was used to determine that the film is actually formed of individual particles with average lateral dimensions of 28 nm ( ± 8 nm). The complex refractive indices of the equivalent uniform film in air at a wavelength of 1570 nm were calculated from the measurements to be 4.84-i0.74 and 3.97-i0.85 for TM and TE polarizations respectively (compared to the value for bulk gold: 0.54-i10.9). Additionally, changes in the birefringence and dichroism of the films were measured as a function of the surrounding medium, in air, water and a saturated NaCl (salt) solution. These results show that the film has stronger dielectric behavior for TM light than for TE, a trend that increases with increasing surrounding index. Finally, the experimental results are compared to predictions from two widely used effective medium approximations, the generalized Maxwell-Garnett and Bruggeman theories for gold particles in a surrounding matrix. It is found that both of these methods fail to predict the observed behavior for the film considered.


Alexithymia: a general deficit of interoception.
Alexithymia is a sub-clinical construct, traditionally characterized by difficulties identifying and describing one's own emotions. Despite the clear need for interoception (interpreting physical signals from the body) when identifying one's own emotions, little research has focused on the selectivity of this impairment. While it was originally assumed that the interoceptive deficit in alexithymia is specific to emotion, recent evidence suggests that alexithymia may also be associated with difficulties perceiving some non-affective interoceptive signals, such as one's heart rate. It is therefore possible that the impairment experienced by those with alexithymia is common to all aspects of interoception, such as interpreting signals of hunger, arousal, proprioception, tiredness and temperature. In order to determine whether alexithymia is associated with selectively impaired affective interoception, or general interoceptive impairment, we investigated the association between alexithymia and self-reported non-affective interoceptive ability, and the extent to which individuals perceive similarity between affective and non-affective states (both measured using questionnaires developed for the purpose of the current study), in both typical individuals (n = 105 (89 female), mean age = 27.5 years) and individuals reporting a diagnosis of a psychiatric condition (n = 103 (83 female), mean age = 31.3 years). Findings indicated that alexithymia was associated with poor non-affective interoception and increased perceived similarity between affective and non-affective states, in both the typical and clinical populations. We therefore suggest that rather than being specifically associated with affective impairment, alexithymia is better characterized by a general failure of interoception.


Adipokines in plasma and breast tissues: associations with breast cancer risk factors.
Blood adipokines are associated with breast cancer risk; however, blood-breast adipokine correlations and factors that explain variation in adipokines are unknown. Plasma (n = 155) and breast (n = 85) leptin and adiponectin were assessed by immunoassays in women with no history of cancer. Multivariable-adjusted regression models were used to determine breast adipokine associations. Through body mass index (BMI)-adjusted analyses, we initially observed positive plasma-breast correlations for leptin (r = 0.41, P = 0.0002) and adiponectin (r = 0.23, P = 0.05). The positive plasma-breast correlation for leptin was strongest among normal weight women (r = 0.62), whereas the correlation for adiponectin was strongest among obese women (r = 0.31). In multivariable models, adjusting for BMI, demographic, reproductive, and lifestyle factors, plasma leptin was not associated with breast leptin, and only the highest quartile of plasma adiponectin was associated with tissue levels. Of the risk factors investigated, those that contributed most to the variation in breast tissue adipokines were BMI and race for leptin, oral contraceptive use and smoking status for adiponectin. Although we report positive plasma-breast adipokine correlations overall, plasma adipokine concentrations may not be good surrogates for breast concentrations among all women. Predictors of breast adipokines vary, depending on subject characteristics, possibly explaining inconsistent epidemiologic results and they implicate differing pathways toward carcinogenesis. A clearer understanding of the relationships between plasma adipokines and their levels within the target organ is necessary to better understand the impact of these hormones on breast cancer risk. Future studies are needed to identify additional factors associated with breast adipokines in target tissues.


The relationship between road traffic accidents and real economic activity in Spain: common cycles and health issues.
This paper analyses the aggregate relationships between traffic accidents and real economic activity in Spain during the last 30 years. Our general approach is based on two basic assumptions: (1) the number of accidents depends on the use of cars and other exogenous variables, and (2) the level of economic activity affects variation in the stock of cars, as well as degree of utilization. We propose a novel turning point characterization for monthly seasonal data that allows to check whether economic and road accident cycles coincide and, to date the beginning and end of their respective cycles. Empirical results from this section are important in establishing posterior causal models and whether or not economic activity and road accidents have a common component in the long run and a varying lead-lag relationship, depending on the cycles. These models will be the basis to check when Spain will achieve the European Union figures in terms of the fatalities/accidents ratio under different scenarios. Empirical results as well as historical experiences from other European countries proved that reducing fatalities is not only a question of diminishing accidents rates.


Ultrafast imaging of laser-controlled non-adiabatic dynamics in NO2 from time-resolved photoelectron emission.
Time-resolving and controlling coupled electronic and nuclear dynamics at conical intersections on the sub-femtosecond to few-femtosecond time scale is among the challenging goals of attosecond physics. Here we present numerical simulations of time-resolved photoelectron spectroscopy of such dynamics in NO2, where the coupled electron-nuclear motion at the 2A1/2B2 conical intersection is steered on the sub-laser-cycle time scale by a nearly single-cycle, waveform controlled mid-infrared laser pulse. For a rigorous description of the photoionization dynamics, we employ ab initio energy- and geometry-resolved photoionization matrix elements obtained with the multichannel R-matrix method, using a multiconfigurational description of the molecule and a newly developed algorithm to generate photoionization dipoles that are phase consistent on the level of both the neutral and the ionic states. We find that for sufficient molecular alignment, the time- and energy-resolved anisotropy parameters of the photoelectron angular distributions provide a particularly clear picture of both the ultrafast natural molecular dynamics at the conical intersection and its modifications by the control pulse. In particular, changes in the electronic and nuclear configurations induced by the control pulse lead to the appearance of non-vanishing odd anisotropy parameters in the photoelectron spectra. These are absent in the spectra obtained without the control pulse and therefore provide sensitive, background-free diagnostic of the control.


The ras-binding domain of ral GDS-like protein-2 as a ras inhibitor in smooth muscle cells.
This study was undertaken to determine whether the response of smooth muscle cells to mitogens can be inhibited by inactivating ras with the ral GDS like protein-2 ras-binding domain (RGL2-RBD). RGL2 is a member of the ral GDS family of proteins that contains a carboxy terminal ras-binding domain which binds the GTP ligated form of ras and rap and a CDC25 homology domain with the structural features of a guanine nucleotide exchange factor. The effect of ras signaling on the smooth muscle cell growth factor response was studied using rat aortic A10 smooth muscle cells transfected with a plasmid that encoded the RGL2-RBD. RGL2-RBD transfection resulted in a 12-fold reduction in the number of clonal colonies that were obtained after selection, and dramatically slowed cell cycle progression. RGBL2-RBD reduced DNA synthesis and inhibited platelet derived growth factor (PDGF)-mediated activation of the MAPK pathway. These findings indicated that interfering with ras signaling inhibits smooth muscle cell proliferation and raise the possibility that ras signaling inhibition might be used therapeutically to control smooth muscle proliferation after vascular injury.


Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor.
Synthetic agonists of the growth hormone secretagogue receptor (GHSR) rejuvenate the pulsatile pattern of GH-release in the elderly, and increase lean but not fat mass in obese subjects. Screening of tissue extracts in a cell line engineered to overexpress the GHSR led to the identification of a natural agonist called ghrelin. Paradoxically, this hormone was linked to obesity. However, it had not been directly shown that the GHSR is a physiologically relevant ghrelin receptor. Furthermore, ghrelin's structure is significantly different from the synthetic agonist (MK-0677) used to expression-clone the GHSR. To address whether the GHSR mediates ghrelin's stimulatory effects on GH release and appetite, we generated Ghsr-null mice. In contrast to wild-type mice, acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. Nevertheless, Ghsr-null mice are not dwarfs; their appetite and body composition are comparable to that of wild-type littermates. Furthermore, in contrast to suggestions that ghrelin regulates leptin and insulin secretion, fasting-induced changes in serum levels of leptin and insulin are identical in wild-type and null mice. Serum insulin-like growth factor 1 levels and body weights of mature Ghsr-null mice are modestly reduced compared to wild-type littermates, which is consistent with ghrelin's property as an amplifier of GH pulsatility and its speculated role in establishing an insulin-like growth factor 1 set-point for maintaining anabolic metabolism. Our results suggest that chronic treatment with ghrelin antagonists will have little effect on growth or appetite.


Resilience and recovery: the effect of triclosan exposure timing during development, on the structure and function of river biofilm communities.
Triclosan (TCS) is a ubiquitous antibacterial agent found in soaps, scrubs, and consumer products. There is limited information on hazardous effects of TCS in the environment. Here, rotating annular reactors were used to cultivate river biofilm communities exposed to 1.8 μg l(-1) TCS with the timing and duration of exposure and recovery during development varied. Two major treatment regimens were employed: (i) biofilm development for 2, 4 or 6 weeks prior to TCS exposure and (ii) exposure of biofilms to TCS for 2, 4 or 6 weeks followed by recovery. Biofilms not exposed to TCS were used as a reference condition. Communities cultivated without and then exposed to TCS all exhibited reductions in algal biomass and significant (p<0.05) reductions in cyanobacterial biomass. No significant effects were observed on bacterial biomass. CLSM imaging of biofilms at 8 weeks revealed unique endpoints in terms of community architecture. Community composition was altered by any exposure to TCS, as indicated by significant shifts in denaturing gradient gel electrophoresis fingerprints and exopolymer composition relative to the reference. Bacterial, algal and cyanobacterial components initially exposed to TCS were significantly different from those TCS-free at time zero. Pigment analyses suggested that significant changes in composition of algal and cyanobacterial populations occurred with TCS exposure. Bacterial thymidine incorporation rates were reduced by TCS exposure and carbon utilization spectra shifted in terms substrate metabolism. Direct counts of protozoans indicated that TCS was suppressive, whereas micrometazoan populations were, in some instances, stimulated. These results indicate that even a relatively brief exposure of a river biofilm community to relatively low levels of TCS alters both the trajectory and final community structure. Although some evidence of recovery was observed, removal of TCS did not result in a return to the unexposed reference condition.


Towards the integration and development of a cross-European research network and infrastructure: the DEterminants of DIet and Physical ACtivity (DEDIPAC) Knowledge Hub.
To address major societal challenges and enhance cooperation in research across Europe, the European Commission has initiated and facilitated 'joint programming'. Joint programming is a process by which Member States engage in defining, developing and implementing a common strategic research agenda, based on a shared vision of how to address major societal challenges that no Member State is capable of resolving independently. Setting up a Joint Programming Initiative (JPI) should also contribute to avoiding unnecessary overlap and repetition of research, and enable and enhance the development and use of standardised research methods, procedures and data management. The Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub (KH) is the first act of the European JPI 'A Healthy Diet for a Healthy Life'. The objective of DEDIPAC is to contribute to improving understanding of the determinants of dietary, physical activity and sedentary behaviours. DEDIPAC KH is a multi-disciplinary consortium of 46 consortia and organisations supported by joint programming grants from 12 countries across Europe. The work is divided into three thematic areas: (I) assessment and harmonisation of methods for future research, surveillance and monitoring, and for evaluation of interventions and policies; (II) determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; and (III) evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours. In the first three years, DEDIPAC KH will organise, develop, share and harmonise expertise, methods, measures, data and other infrastructure. This should further European research and improve the broad multi-disciplinary approach needed to study the interactions between multilevel determinants in influencing dietary, physical activity and sedentary behaviours. Insights will be translated into more effective interventions and policies for the promotion of healthier behaviours and more effective monitoring and evaluation of the impacts of such interventions.


School and work status, drug-free workplace protections, and prescription drug misuse among Americans ages 15-25.
We assessed the prevalence and characteristics of prescription drug misuse among youth ages 15-25 to examine differences by student and employment status, and associations with workplace antidrug policies and programs. Multivariate logistic regressions analyzed associations in weighted data on the 20,457 young adults in the combined 2004-2008 National Surveys on Drug Use and Health. Demographic controls included sex, race, community size, and age group. After we accounted for demographic controls, at ages 15-25, students were less likely than nonstudents to misuse prescription drugs. Segmenting student from nonstudent groups, working consistently was associated with a further reduction in misuse for those ages 18-25. When we controlled for demographics and substance use history, both Employee Assistance Program (EAP) services and awareness that one's employer had a drug-free workplace policy were associated with significantly lower misuse of prescription drugs (OR = 0.85 for each program, 95% CI [0.73, 1.00] and [0.72, 1.00]). Associations of workplace antidrug policies and programs with marijuana use and with Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria for alcohol abuse and dependence contrasted sharply with these patterns. All four aspects were significantly associated with lower marijuana use. None was associated with problem drinking. Protective effects of drug-free workplace policy and EAPs persist after other substance use was controlled for. Comparing the effects of workplace programs on illicit drug use and problem drinking versus prescription misuse suggests that those protective associations do not result from selection bias. Thus, drug-free workplace policies and EAPs appear to help protect younger workers against prescription misuse. If workplace substance use disorder programs focused prevention messages and interventions on prescription drug misuse, their impact on misuse might increase.


Severity of the COVID-19 pandemic in India.
The main objective of this study is to identify the socioeconomic, meteorological, and geographical factors associated with the severity of COVID-19 pandemic in India. The severity is measured by the cumulative severity ratio (CSR)-the ratio of the cumulative COVID-related deaths to the deaths in a pre-pandemic year-its first difference and COVID infection cases. We have found significant interstate heterogeneity in the pandemic development and have contrasted the trends of the COVID-19 severities between Maharashtra, which had the largest number of COVID deaths and cases, and the other states. Drawing upon random-effects models and Tobit models for the weekly and monthly panel data sets of 32 states/union territories, we have found that the factors associated with the COVID severity include income, gender, multi-morbidity, urbanization, lockdown and unlock phases, weather including temperature and rainfall, and the retail price of wheat. Brief observations from a policy perspective are made toward the end.


Prevalence of dental trauma and mouthguard awareness among weekend warrior soccer players.
Traumatic dental and facial injuries are frequent in sports and often cause esthetic, functional, psychological, and economic problems. The term "weekend warrior" is used to describe people who participate in physically demanding activities only on the weekend, or part-time. In this prospective cohort study, we examined the prevalence of dental trauma and knowledge of traumatic dental injuries among weekend warriors in Ankara, Turkey. A detailed questionnaire on mouthguard awareness and knowledge and experience of dental trauma was distributed to 1,007 weekend warrior athletes participating in a soccer tournament. The results showed that 9.8% of participants had experienced orofacial trauma, 21.7% were aware of mouthguards, 2.9% reported using mouthguards, 15.4% were aware of the field of sports dentistry, and 19.6% were aware of emergency treatment for dental trauma. Participation in sports, especially contact sports, greatly increases the risk of dental injury. The present results show that knowledge of traumatic orofacial and dental injuries is limited among weekend warriors. Public health authorities should develop relevant educational programs, including broad dissemination of information on the risks of traumatic dental injuries and methods for protection against such injuries.


[Renal manifestation of Autosomal Dominant Polycystic Kidney Disease].
Autosomal dominant polycystic kidney disease affects over 12 million people in the world and is the fourth cause of ESRD. It is the main monogenic kidney disease and causes the progressive formation of cysts leading to renal failure after a few decades. The main manifestations of the disease are observed even at a young age. The early sign of ADPKD is impaired urinary concentrating capacity, due to medullary alteration by cysts, and resistance to vasopressin. These anatomical alterations determine hyperfiltration, altered ammonium transport, nephrolithiasis, and, above all, hypertension even in pediatric age. Activation of the renin-angiotensin-aldosterone system has been shown responsible for the maintenance of high pressure values as well as the growth of cysts and renal fibrosis. Arterial hypertension would be responsible for ventricular hypertrophy. Many recent studies have confirmed the role of pressure control, especially if rigorous, in decreasing the progression of renal disease, and the use of ACE inhibitors seems to have higher efficacy than other antihypertensive drugs. The progression of renal disease is evidenced by the reduction of glomerular filtration which may be minimal in the early years, due to hyperfiltration, but, then, may even exceed 5 ml / min per year, especially when the total kidney volume (TKV) exceeds 1500 ml. In more rapid progression forms, ESRD may appear at about 55 years of age. The main risk factors are age, genetic mutation, familiarity with ESRD, macrohematuria episodes, and early onset hypertension. Some authors have proposed both genetic and clinical scores that can provide guidance on the probability of rapid progression. Other renal manifestations include kidney pain, nephrolithiasis, urinary tract infections and cyst hemorrhage. Renal cell carcinoma is a very rare event.


Autoimmune dementia: clinical course and predictors of immunotherapy response.
To define the diagnostic characteristics and predictors of treatment response in patients with suspected autoimmune dementia. Between January 1, 2002, and January 1, 2009, 72 consecutive patients received immunotherapy for suspected autoimmune dementia. Their baseline clinical, radiologic, and serologic characteristics were reviewed and compared between patients who were responsive to immunotherapy and those who were not. Patients were classified as responders if the treating physician had reported improvement after immunotherapy (documented in 80% by the Kokmen Short Test of Mental Status, neuropsychological testing, or both). Initial immunotherapeutic regimens included methylprednisolone in 56 patients (78%), prednisone in 12 patients (17%), dexamethasone in 2 patients (3%), intravenous immune globulin in 1 patient (1%), and plasma exchange in 1 patient (1%). Forty-six patients (64%) improved, most in the first week of treatment. Thirty-five percent of these immunotherapy responders were initially diagnosed as having a neurodegenerative or prion disorder. Pretreatment and posttreatment neuropsychological score comparisons revealed improvement in almost all cognitive domains, most notably learning and memory. Radiologic or electroencephalographic improvements were reported in 22 (56%) of 39 patients. Immunotherapy responsiveness was predicted by a subacute onset (P<.001), fluctuating course (P<.001), tremor (P=.007), shorter delay to treatment (P=.005), seropositivity for a cation channel complex autoantibody (P=.01; neuronal voltage-gated potassium channel more than calcium channel or neuronal acetylcholine receptor), and elevated cerebrospinal fluid protein (>100 mg/dL) or pleocytosis (P=.02). Of 26 immunotherapy-responsive patients followed up for more than 1 year, 20 (77%) relapsed after discontinuing immunotherapy. Identification of clinical and serologic clues to an autoimmune dementia allows early initiation of immunotherapy, and maintenance if needed, thus favoring an optimal outcome.


Medication-Related Factors and Hospital Readmission in Older Adults with Chronic Kidney Disease.
This study aimed to examine the association between medication-related factors and risk of hospital readmission in older patients with chronic kidney disease (CKD). A retrospective analysis was conducted targeting older CKD (n = 204) patients admitted to an Australian hospital. Medication appropriateness (Medication Appropriateness Index; MAI), medication regimen complexity (number of medications and Medication Regimen Complexity Index; MRCI) and use of selected medication classes were exposure variables. Outcomes were occurrence of readmission within 30 and 90 days, and time to readmission within 90 days. Logistic and Cox hazards regression were used to identify factors associated with readmission. Overall, 50 patients (24%) were readmitted within 30 days, while 81 (40%) were readmitted within 90 days. Mean time to readmission within 90 days was 66 (SD 34) days. Medication appropriateness and regimen complexity were not independently associated with 30- or 90-day hospital readmissions in older adults with CKD, whereas use of renin‒angiotensin blockers was associated with reduced occurrence of 30-day (adjusted OR 0.39; 95% CI 0.19⁻0.79) and 90-day readmissions (adjusted OR 0.45; 95% CI 0.24⁻0.84) and longer time to readmission within 90 days (adjusted HR 0.52; 95% CI 0.33⁻0.83). This finding highlights the importance of considering the potential benefits of individual medications during medication review in older CKD patients.


In vitro and in vivo lipolysis of plasma triglycerides increases the resistance to oxidative modification of low-density lipoproteins.
The majority of studies on low-density lipoprotein (LDL) particle size and susceptibility to oxidative modification have been either descriptive or interventional, but there are few mechanistic studies. Effects of exhaustive in vitro and in vivo lipolysis of serum and plasma triglycerides, respectively, by lipoprotein lipase (LPL) were investigated in healthy normotriglyceridemic men. The LDL end-product of lipolysis of very low-density lipoprotein (VLDL) underwent compositional analysis, gradient gel electrophoresis and an assessment of resistance to copper-induced oxidative modification. The LDL particle contents of free fatty acid and alpha-tocopherol increased, whereas the contents of free and esterified cholesterol, alpha-carotene and coenzyme Q10 decreased upon incubation of serum with LPL in vitro. The LDL particle size decreased and the resistance to the oxidative modification of LDL increased. Lipolysis of plasma triglycerides in vivo, achieved by intravenous injection of heparin, did not alter the LDL particle size but increased the resistance to the oxidative modification of LDL. This change was accompanied by an increase in the LDL particle content of alpha-tocopherol, whereas the free fatty acid content was unaltered. The results show that the increased resistance to oxidative modification of LDL after lipolysis of plasma triglycerides was concomitant with an increased LDL particle content of alpha-tocopherol, and that free fatty acids did not seem to contribute to the increased resistance to oxidative modification of LDL in vivo. Furthermore, our data indicate that the resistance of LDL to oxidative modification is not dependent on particle size.


Sigmoid motility in diverticular disease and the irritable bowel syndrome.
Intraluminal pressures were measured with four open ended, water perfused tubes in the fasting state and after a standard liquid meal (400 KCal, 375 ml, protein 15 g, carbohydrate 55 g, lipid 13.4 g) in six patients with sigmoid diverticular disease, 20 with the irritable bowel syndrome and in 13 controls. The pressure sensors were positioned in the true sigmoid colon at colonoscopy at 25, 35, 45, and 55 cm from the anus. Colonic pressures were significantly higher in diverticular disease than in controls before (p less than 0.02) and after the meal (p less than 0.002), some pressure amplitudes exceeding 300 cm H2O. Patients with the irritable bowel syndrome had lower (p less than 0.05) pressures than controls before the meal. Postprandial sigmoid pressures were within the mean +/- 2 SD of controls in 10, above in two and below in eight patients with the irritable bowel. Hypercontractility of the sigmoid colon in the irritable bowel syndrome was not confirmed under the conditions of this study. The association between sigmoid diverticulosis and high intraluminal pressures is confirmed.


Treatment satisfaction in osteoarthritis and chronic low back pain: the role of pain, physical and emotional functioning, sleep, and adverse events.
Global ratings of treatment satisfaction and improvement can provide an opportunity for patients to aggregate multiple aspects of their treatment into a single measure of its perceived benefits and disadvantages. Although such measures have been recommended for chronic pain clinical trials, only limited data are available that address the hypothesis that they reflect multiple aspects of patients' treatment experience. Our objective was to identify the factors that make independent contributions to ratings of treatment satisfaction. We analyzed data from 5 open-label clinical trials of lidocaine patch 5% in osteoarthritis knee pain and chronic low back pain that were 2 to 12 weeks in duration. A total of 383 patients completed the Patient Global Assessment of Treatment Satisfaction scale and measures of pain, interference with physical and emotional functioning, sleep interference, and adverse events. The results of multivariate analyses indicated that improvements in measures of pain intensity, pain relief, and interference with physical functioning each made independent contributions to treatment satisfaction in both groups of patients. Improvements in interference with emotional functioning and sleep and the presence and severity of adverse events were not associated with satisfaction. Measures of treatment satisfaction can reflect different aspects of the patient's treatment response, including improvements in pain and physical functioning. Increased understanding of such global measures may facilitate development of clinical trial outcomes that allow patients to evaluate with minimal burden those aspects of the treatment experience they consider personally meaningful.


Paradoxical risk perception and behaviours related to Avian Flu outbreak and education campaign, Laos.
In Laos, small backyard poultry systems predominate (90%). The first lethal human cases of highly pathogenic avian influenza (HPAI) occurred in 2007. Few studies have addressed the impact of outbreaks and education campaigns on a smallholder producer system. We evaluated awareness and behaviours related to educational campaigns and the 2007 HPAI outbreaks. During a national 2-stage cross-sectional randomised survey we interviewed 1098 households using a pre-tested questionnaire in five provinces representative of the Southern to Northern strata of Laos. We used multivariate analysis (Stata, version 8; Stata Corporation, College Station, TX, USA) to analyse factors affecting recollection of HPAI educational messages, awareness of HPAI, and behaviour change. Of the 1098 participants, 303 (27.6%) received training on HPAI. The level of awareness was similar to that in 2006. The urban population considered risk to be decreased, yet unsafe behaviours persisted or increased. This contrasted with an increase in awareness and safe behaviour practices in rural areas. Reported behaviour changes in rural areas included higher rates of cessation of poultry consumption and dead poultry burial when compared to 2006. No participants reported poultry deaths to the authorities. Overall, 70% could recall an educational message but the content and accuracy differed widely depending on training exposure. Washing hands and other hygiene advice, messages given during the HPAI educational campaign, were not recalled. Trained persons were able to recall only one message while untrained participants recalled a broader range of messages. Factors associated with an awareness of a threat of AI in Laos were: having received HPAI training, literacy level, access to TV, recent information, living in rural areas. We report a paradoxical relationship between unsafe behaviours and risk perception in urban areas, as well as exposure to HPAI training and message misinterpretation. Future educational campaigns need to be tailored to specific target populations and farming styles, for example, small holder farms as compared to commercial farms. Special attention must be given to varying risk perceptions and the risk of misinterpretation of key messages, economic hardship, and real life consequences of reporting.


Regional variations in ambulatory care and incidence of cardiovascular events.
Variations in the prevalence of traditional cardiac risk factors only partially account for geographic variations in the incidence of cardiovascular disease. We examined the extent to which preventive ambulatory health care services contribute to geographic variations in cardiovascular event rates. We conducted a cohort study involving 5.5 million patients aged 40 to 79 years in Ontario, Canada, with no hospital stays for cardiovascular disease as of January 2008, through linkage of multiple population-based health databases. The primary outcome was the occurrence of a major cardiovascular event (myocardial infarction, stroke or cardiovascular-related death) over the following 5 years. We compared patient demographics, cardiac risk factors and ambulatory health care services across the province's 14 health service regions, known as Local Health Integration Networks (LHINs), and evaluated the contribution of these variables to regional variations in cardiovascular event rates. Cardiovascular event rates across LHINs varied from 3.2 to 5.7 events per 1000 person-years. Compared with residents of high-rate LHINs, those of low-rate health regions received physician services more often (e.g., 4.2 v. 3.5 mean annual family physician visits, p value for LHIN-level trend = 0.01) and were screened for risk factors more often. Low-rate LHINs were also more likely to achieve treatment targets for hypercholes-terolemia (51.8% v. 49.6% of patients, p = 0.03) and controlled hypertension (67.4% v. 53.3%, p = 0.04). Differences in patient and health system factors accounted for 74.5% of the variation in events between LHINs, of which 15.5% was attributable to health system factors alone. Preventive ambulatory health care services were provided more frequently in health regions with lower cardiovascular event rates. Health system interventions to improve equitable access to preventive care might improve cardiovascular outcomes.